Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine.

Introduction: The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters.

Methods: Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways.

Lipoprotein Profile in Immunological Non-Responders PLHIV after Antiretroviral Therapy Initiation.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART).

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients).

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4 T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy.

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4 T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4 T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL).

In vivo dosimetry in low-voltage IORT breast treatments with XR-RV3 radiochromic film.

Purpose: The objectives of the study were to establish a procedure for in vivo film-based dosimetry for intraoperative radiotherapy (IORT), evaluate the typical doses delivered to organs at risk, and verify the dose prescription.

Materials And Methods: In vivo dose measurements were studied using XR-RV3 radiochromic films in 30 patients with breast cancer undergoing IORT using the Axxent® device (Xoft Inc.).

High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients.

Background: The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4T-cell turnover.

Methods: We evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-α/CCL3, MIP-β/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery.

Findings: The circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864_814) were associated with immune recovery status.

Adjuvant breast radiotherapy, endocrine therapy, or both after breast conserving surgery in older women with low-risk breast cancer: Results from a population-based study.

Background And Purpose: The relative benefit of adjuvant radiotherapy (RT) alone in older women with low-risk early breast cancer (EBC) remains unclear. It is hypothesized that adjuvant RT-alone can improve outcomes of older patients with low-risk EBC, similar to endocrine therapy (ET) alone or combination of RT + ET.

Methods: In this population based study, we identified all women aged ≥70 with T1-2, N0, ER+ve, Her-2/neu-ve EBC treated with breast conserving surgery (BCS), followed by adjuvant treatments (RT-alone, ET-alone, or RT + ET combination) from 2005 to 2015.

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status.

A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4 T-cell recovery in HIV-infected subjects.

Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection.

Background: Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control.

Proteomic Profile Associated With Loss of Spontaneous Human Immunodeficiency Virus Type 1 Elite Control.

Background: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers.

Circulating metabolomic profile can predict dyslipidemia in HIV patients undergoing antiretroviral therapy.

Background And Aims: Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes.

Methods: To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months.

A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients.

Objectives: Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response.

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels.

Background And Objectives: Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163.

Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).

Objectives: A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

Objectives: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs.

Lipodystrophy and insulin resistance in combination antiretroviral treated HIV-1-infected patients: implication of resistin.

Background: Little information is available with respect to the involvement of resistin in lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with combination antiretroviral therapy (cART). We determined whether the resistin (rest) -420C>G single-nucleotide polymorphism and plasma resistin are associated with the development of lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with cART.

Methods: The study group comprised 299 HIV-1-infected patients treated with a stable cART for at least 1 year (143 with lipodystrophy and 156 without) and 175 uninfected controls.

In vitro activity of nadifloxacin against several Gram-positive bacteria and analysis of the possible evolution of resistance after 2 years of use in Germany.

Nadifloxacin has good activity against Propionibacterium acnes as well as against both meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) and Staphylococcus epidermidis. The aim of this study was to evaluate the activity of this fluoroquinolone against the abovementioned microorganisms, comparing isolates collected in 2007 in Germany, a country where nadifloxacin has been used for the last 2 years, with isolates collected from 2006-2007 in Spain where nadifloxacin has not been used. A collection of P.

In vitro activity of doripenem against Acinetobacter baumannii clinical isolates.

Doripenem is a carbapenem with activity against Gram-positive and Gram-negative pathogens. This study evaluated the in vitro activity of doripenem against a collection of 87 Acinetobacter baumannii clinical isolates, showing that the activity of doripenem was superior to imipenem and meropenem for strains carrying the bla(OXA-58) gene. A.

Characterization of the carbapenem-hydrolyzing oxacillinase oxa-58 in an Acinetobacter genospecies 3 clinical isolate.

Based on imipenem resistance in an Acinetobacter genospecies 3 clinical isolate, we were able to identify, for the first time in this genomic species, a plasmid-encoded bla(OXA-58) gene that was 100% homologous to the same gene in Acinetobacter baumannii.

Characterization of the carbapenem-hydrolyzing oxacillinase OXA-58 in an Acinetobacter phenon 6/ct13TU clinical isolate.

The bla(OXA-58) gene identified in the Acinetobacter phenon 6/ct13TU clinical isolate presented 100% homology with the same gene in Acinetobacter baumannii. Its location in a plasmid suggests that these resistance genes may be transferred from 1 species to another.

Chicano-Latino Youth Leadership Institute: an asset-based program for youth.

Objective: To describe the theory of action that links the Chicano-Latino Youth Leadership Institute with positive youth development and to highlight promising practices.

Methods: A logic model provided the basis for data collection through written surveys, focus groups, reflection forms, and analysis of Minnesota Student Survey Results.

Results: Primary participant outcomes include increased levels of community service, improved peer relationships, and higher graduation rates than those of Chicano-Latino non-participants.